Beware of nonconvulsive seizures in prolonged disorders of consciousness: Long-term EEG monitoring is the key.

OBJECTIVE: Evaluate the prevalence of epileptic seizures (ES) and epileptiform discharges (EDs) in patients with prolonged disorders of consciousness (DOC), and potential influence of amantadine on epilepsy. METHODS: We conducted a retrospective study in 34 patients hospitalized in a DOC care unit for prolonged DOC between 2012 and 2018, who received a long-term EEG monitoring (LTM). We reviewed the prevalence of ES, EDs and nonconvulsive seizures (NCSz), the type of DOC recovery treatment administered, and neurological outcome. RESULTS: LTM was more effective than standard EEGs in detecting EDs (32% vs 21% respectively). Moreover, 12% of the LTM showed NCSz. Among patients with EDs in LTM, 73% showed no EDs in standard EEG recordings, even when performed more than once. The presence of EDs and/or NCSz in LTM was significantly associated with the occurrence of remote clinical epileptic seizures (p = 0.017) but did not influence neurological outcome (p = 1). Amantadine was not associated with higher occurrence of EDs/NCSz or clinical seizures. CONCLUSION: In our prolonged DOC population, LTM showed more pathological results (EDs and NCSz) than standard EEGs, which was significantly associated with remote clinical seizures. SIGNIFICANCE: The use of LTM might be advised to rule out NCSz in patients with prolonged DOC.

Anterior thalamic nucleus deep brain stimulation for refractory epilepsy: Preliminary results in our first 5 patients.

OBJECTIVES: Deep brain stimulation (DBS) of the anterior thalamic nucleus (ATN) has been recognized to be an efficient treatment of refractory epilepsy (RE). However, ATN targeting is difficult and up to 8% of lead misplacement is reported. Our objective is to report our surgical procedure based on MRI targeting and our clinical results. PATIENTS AND METHODS: Our first five consecutive patients (4M, 1F, mean age: 42.8 years) treated by DBS of ATN between March and October 2016 were included. The mean duration of their epilepsy was 29 years. Four patients had already vagal nerve stimulation and 2 mammillary body stimulation. Stereotactic coordinates were calculated using distal segment of mammillothalamic tract as landmark. All procedures were performed under general anesthesia with intraoperative control of lead position using a robotic 3D fluoroscopy and image fusion with the preoperative MRI. RESULTS: No complications or lead misplacement was observed. The mean 3D distance between the planned target and location of the lead was 1.8 mm. Each patient was followed up at least one year (15+3months). The stimulation parameters were: 140Hz, 90m/s and 5 Volts with one minute ON/five minutes OFF cycle. The mean reduction of seizure frequency reached -52.5% (+32.2) at 6-months but decreased to -24.5% (+65.7) at the last follow-up due to some adverse events not related to stimulation. CONCLUSION: No complication, no lead misplacement and the improvement in our first patients, previously not help by multiple medications or surgeries, are encouraging.

Intensity-dependent modulatory effects of vagus nerve stimulation on cortical excitability.

OBJECTIVES: Vagus nerve stimulation (VNS) is an effective treatment for refractory epilepsy. It remains unknown whether VNS efficacy is dependent on output current intensity. The present study investigated the effect of various VNS output current intensities on cortical excitability in the motor cortex stimulation rat model. The hypothesis was that output current intensities in the lower range are sufficient to significantly affect cortical excitability. MATERIAL AND METHODS: VNS at four output current intensities (0 mA, 0.25 mA, 0.5 mA and 1 mA) was randomly administered in rats (n = 15) on four consecutive days. Per output current intensity, the animals underwent five-one-hour periods: (i) baseline, (ii) VNS1, (iii) wash-out1, (iv) VNS2 and (v) wash-out2. After each one-hour period, the motor seizure threshold (MST) was measured and compared to baseline (i.e. ∆MSTbaseline , ∆MSTVNS 1 , ∆MSTwash-out1 , ∆MSTVNS 2 and ∆MSTwash-out2 ). Finally, the mean ∆MSTbaseline , mean ∆MSTwash-out1 , mean ∆MSTwash-out2 and mean ∆MSTVNS per VNS output current intensity were calculated. RESULTS: No differences were found between the mean ∆MSTbaseline , mean ∆MSTwash-out1 and mean ∆MSTwash-out2 within each VNS output current intensity. The mean ∆MSTVNS at 0 mA, 0.25 mA, 0.5 mA and 1 mA was 15.3 ± 14.6 µA, 101.8 ± 23.5 µA, 108.1 ± 24.4 µA and 85.7 ± 18.1 µA respectively. The mean ∆MSTVNS at 0.25 mA, 0.5 mA and 1 mA were significantly larger compared to the mean ∆MSTVNS at 0 mA (P = 0.002 for 0.25 mA; P = 0.001 for 0.5 mA; P = 0.011 for 1 mA). CONCLUSIONS: This study confirms efficacy of VNS in the motor cortex stimulation rat model and indicates that, of the output current intensities tested, 0.25 mA is sufficient to decrease cortical excitability and higher output current intensities may not be required.

Modulation of seizure threshold by vagus nerve stimulation in an animal model for motor seizures.

OBJECTIVE: The precise mechanism of action of vagus nerve stimulation (VNS) in suppressing epileptic seizures remains to be elucidated. This study investigates whether VNS modulates cortical excitability by determining the threshold for provoking focal motor seizures by cortical electrical stimulation before and after VNS. MATERIAL AND METHODS: Male Wistar rats (n = 8) were implanted with a cuff-electrode around the left vagus nerve and with stimulation electrodes placed bilaterally on the rat motor cortex. Motor seizure threshold (MST) was assessed for each rat before and immediately after 1 h of VNS with standard stimulation parameters, during two to three sessions on different days. RESULTS: An overall significant increase of the MST was observed following 1 h of VNS compared to the baseline value (1420 microA and 1072 microA, respectively; P < 0.01). The effect was reproducible over time with an increase in MST in each experimental session. CONCLUSIONS: VNS significantly increases the MST in a cortical stimulation model for motor seizures. These data indicate that VNS is capable of modulating cortical excitability.

Increased rat serum corticosterone suggests immunomodulation by stimulation of the vagal nerve.

The role of the vagal nerve within the immune system has not been fully elucidated. Vagal afferents connect to several central nervous system structures, including the hypothalamus. We investigated the effect of vagal nerve stimulation (VNS) on serum corticosterone levels in rats. Corticosterone levels were measured following 1 h of high frequency (30 Hz) or low frequency (1 Hz) VNS in awake animals. There was a significant increase (p < 0.05) in serum corticosterone levels following 30 Hz VNS compared to 1 Hz VNS or sham stimulation. These results suggest an immediate effect of VNS on the hypothalamic pituitary-adrenal (HPA) axis and support the role of the vagal nerve in immunomodulation.